Identification of a virus intein and a possible variation in the protein-splicing reaction

Inteins are protein ‘introns’ found inside other proteins. They remove themselves from their host proteins post-translationally in an autoproteolytic protein-splicing reaction [1]. Besides their proteinsplicing activity, many inteins also have endonucleolytic activity believed to mediate the homing of their genes to corresponding unoccupied integration sites. Both functions benefit the inteins: protein splicing averts deleterious effects caused by their insertion into the protein hosts and homing disseminates inteins by horizontal gene transfer. Inteins therefore appear to be selfish genetic elements [2]. Organisms from all three kingdoms of life — eucarya, bacteria and archaea — contain inteins, but their distribution is sporadic. The presence of inteins in evolutionarily distant organisms and their variable appearance in related organisms is generally explained by horizontal transfer [3,4]. The extent of intein horizontal transfer has health implications: Mycobacterium tuberculosis, Mycobacterium leprae and Candida tropicalis are major human pathogens that contain inteins [3]. Here, I describe the first identified insect virus intein. On the basis of the sequence relation of the viral intein and its protein host to other proteins, I propose viruses as vehicles of intein dispersion. A new type of residue in the intein’s carboxyterminal end suggests a variation of the protein-splicing mechanism. The ribonucleotide reductase (RNR) large subunit of the Chilo iridescent virus (CIV) contains an intein. CIV is an insect-infecting iridovirus [5]; members of this double-stranded DNA virus family are known to infect invertebrates, amphibia and fish [6]. All the expected protein-splicing motifs are found in the intein together with the typical dodecapeptide LAGLIDADG homingendonuclease domain (Figure 1a). The glutamine at the carboxyterminal intein end, where only asparagine has been observed before, indicates a variation on the previously described protein-splicing mechanism (see below). RNRs catalyze the essential reaction producing deoxyribonucleotides from ribonucleotides. Three classes of RNRs have been described, distinguished by their sequence, subunit composition and cofactors. Nevertheless, enzymatic mechanism, allosteric control and subtle sequence R634 Current Biology, Vol 8 No 18